title: Pharmacokinetics and 48-week safety and antiviral activity of fosamprenavir-containing regimens in HIV-infected 2- to 18-year-old children.
abstract: BACKGROUND
  Pharmacokinetics, safety and antiviral activity of twice-daily fosamprenavir with or without ritonavir were evaluated in 2- to 18-year-old protease inhibitor-naïve and -experienced HIV-1-infected children.
  
  
  METHODS
  Serial pharmacokinetic samples were collected at week 2 and predose samples every 4-12 weeks. Safety and plasma HIV-1 RNA were monitored every 4-12 weeks.
  
  
  RESULTS
  Twenty protease inhibitor-naïve 2- to <6-year-old subjects received antiretroviral treatment including unboosted fosamprenavir twice-daily, whereas 89 protease inhibitor-naïve and -experienced 2- to 18-year-old subjects received fosamprenavir/ritonavir-containing therapy twice-daily. Median fosamprenavir exposure was 891 days (range 15-1805 days), with 88% exposed >48 weeks. Twice-daily doses of fosamprenavir/ritonavir 23/3 mg/kg in 2- to <6-year olds, 18/3 mg/kg in ≥6-year olds and 700/100 mg in adolescents achieved plasma amprenavir exposures comparable with or higher than 700/100 mg twice-daily in adults while fosamprenavir 30 mg/kg twice-daily in 2- to <6-year olds led to exposures higher than 1400 mg twice-daily in adults. The proportion of subjects with HIV-1 RNA <400 copies/mL at week 48 was 60% for fosamprenavir and 53-74% for fosamprenavir/ritonavir (intent-to-treat [exposed], snapshot analysis). Median increases in absolute and relative (percentage) CD4 counts from baseline to week 48 occurred in both the fosamprenavir (340 cells/mm; 8%) and fosamprenavir/ritonavir group (190 cells/mm; 8%). The most common adverse events were vomiting, cough, and diarrhea; 18 subjects experienced serious adverse events, including 9 with suspected abacavir hypersensitivity.
  
  
  CONCLUSIONS
  Fosamprenavir regimens administered to HIV-1-infected children aged 2-18 years were generally well-tolerated and provided sustained antiviral activity over 48 weeks, with plasma amprenavir exposures comparable with or higher than adults.
authors.affiliation: From the *Sant Joan de Déu Hospital, Barcelona, Spain; †Dr. Victor Babes Hospital for Infectious and Tropical Diseases, Bucharest, Romania; ‡GlaxoSmithKline, Uxbridge, United Kingdom; §GlaxoSmithKline, Research Triangle Park, NC; ¶Tygerberg Children's Hospital, Tygerberg, South Africa; and ‖Hospital Infantil La Fe, Valencia, Spain.
authors.forename: Claudia
authors.initials: C
authors.lastname: Fortuny
authors.forename: Dan
authors.initials: D
authors.lastname: Duiculescu
authors.forename: Katharine
authors.initials: K
authors.lastname: Cheng
authors.forename: Harmony P
authors.initials: HP
authors.lastname: Garges
authors.forename: Mark
authors.initials: M
authors.lastname: Cotton
authors.forename: Desamparados Pérez
authors.initials: DP
authors.lastname: Tamarirt
authors.forename: Susan L
authors.initials: SL
authors.lastname: Ford
authors.forename: Mary Beth
authors.initials: MB
authors.lastname: Wire
authors.forename: Naomi
authors.initials: N
authors.lastname: Givens
authors.forename: Lisa L
authors.initials: LL
authors.lastname: Ross
authors.forename: Yu
authors.initials: Y
authors.lastname: Lou
authors.forename: Teodora
authors.initials: T
authors.lastname: Perger
authors.forename: Jörg
authors.initials: J
authors.lastname: Sievers
mesh_terms: D000293:Adolescent; D019380:Anti-HIV Agents / Q000008:administration & dosage / Q000009:adverse effects* / Q000097:blood / Q000493:pharmacokinetics*; D018791:CD4 Lymphocyte Count; D002219:Carbamates / Q000008:administration & dosage / Q000009:adverse effects* / Q000097:blood / Q000493:pharmacokinetics*; D002648:Child; D002675:Child, Preschool; D005260:Female; D005663:Furans; D015658:HIV Infections / Q000097:blood / Q000188:drug therapy* / Q000378:metabolism* / Q000821:virology; D015497:HIV-1 / Q000235:genetics / Q000302:isolation & purification*; D006801:Humans; D008297:Male; D010755:Organophosphates / Q000008:administration & dosage / Q000009:adverse effects* / Q000097:blood / Q000493:pharmacokinetics*; D012367:RNA, Viral / Q000097:blood; D019438:Ritonavir / Q000008:administration & dosage; D013449:Sulfonamides / Q000008:administration & dosage / Q000009:adverse effects* / Q000097:blood / Q000493:pharmacokinetics*; D019562:Viral Load
chemical_list: D019380:Anti-HIV Agents; D002219:Carbamates; D005663:Furans; D010755:Organophosphates; D012367:RNA, Viral; D013449:Sulfonamides; D019438:Ritonavir; C426859:fosamprenavir